Effect of growth hormone-secreting tumours on skeletal muscle cellularity in the rat

Abstract

Tumours secreting GH (GH1) or GH plus prolactin (GH3) were induced in young (1-week-old) and mature (17-week-old) female Wistar-Furth rats. Young animals were killed at 11 weeks and mature rats at 30 weeks of age. Induction of tumours increased serum GH concentrations and body and soleus muscle weights when compared with those of control rats. The soleus and extensor digitorum longus (EDL) muscles were examined in transverse section by electron microscopy. The percentages of myofibres with myonuclei and with satellite cell nuclei present in both the soleus and EDL muscles were generally greater in young rats with tumours than in young control rats. The percentage of myofibres in the EDL muscle with myonuclei present was higher in mature rats with GH1 tumours compared with age-matched controls. The presence of tumours did not affect the number of fibres in the soleus muscle of either young or mature rats. It was concluded that increased GH concentrations increased muscle weight by increasing the DNA content of myofibres and by myofibre hypertrophy. The rate of proliferation of satellite cells apparently exceeded the rate of incorporation of daughter nuclei into the fibres of the young tumour-bearing rats when compared with that of young controls. Thus, the factors regulating satellite cell proliferation and nuclear incorporation into the myofibre do not appear to be directly coupled.

Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development

“…Although this has been proposed using cell lines in vitro (Morikawa et al 1982;Nixon & Green, 1984;Green et al 1985), attempts to repro¬ duce such findings with primary cell cultures in vitro have proved unsuccessful (Broad & Ham, 1984;Harrison et al 1985; Serrerò & Mills, 1987). In an in-vivo study, McCusker et al (1986) failed to demon¬ strate any effect of GH or GH3 tumours (which secrete GH) implanted into rats on adipose tissue cellularity, although the tumours did decrease the weight of the parametrial fat pad (presumably by inducing lipolysis and producing a decrease in adipocyte cell volume). Although these results appear to disagree with the current study, this could be due to methodol¬ ogical limitations combined with the dual action of GH to stimulate adipocyte differentiation on the one hand, whilst causing fat mobilization (and hence a decrease in adipocyte volume) on the other (see Vernon & Flint, 1989).…”

“…They include measurements using tissue sections in which cells are not spherical and thus volume determination becomes difficult, and cells which have been fixed in osmium tetroxide and digested with collagenase and then counted using Coulter counting techniques. The study of McCusker et al (1986) involved the latter technique and this suffers from two limitations. First, the washing step involves unavoidable loss of smaller cells and secondly Coulter counting normally has a lower cut-off point which ignores smaller cells.…”

The Metabolic Actions of Growth Hormone

“…Long-term (8 wk) treatment of rats with antiserum to rat GH resulted in an 80% decrease in the number of differentiated fat cells in intra-abdominal depots and a 20% decrease in subcutaneous fat (244). Excessive GH, however, apparently does not increase adipogenesis, since the parametrial fat pads of rats bearing GH-secreting tumors were decreased in mass but adipocyte cell number was unchanged from control levels (538).…”

Manipulation of muscle mass

“…No direct effect of GH on muscle cell proliferation or on the metabolism of mammalian satellite cells have been demonstrated in vitro (Gospodarowicz et al 1976;Ewton and Florini, 1980) but IGF-1 has clearly been shown to stimulate cell proliferation, amino acid and glucose uptake and protein synthesis in foetal and post-natal muscle cultures and satellite cells (Florini et al 1977;Harper et al 1987;Roe et al 1989). McCusker and Campion (1986) showed that increased soleus muscle weights observed in rats with GH-secreting tumours were due to elevated DNA content of the myofibres and to myofibre hypertrophy. McCusker and Campion (1986) showed that increased soleus muscle weights observed in rats with GH-secreting tumours were due to elevated DNA content of the myofibres and to myofibre hypertrophy.…”